Passive Cavitation Image-Guided Ultrasound-Mediated Drug Delivery for Atheroma Th

被动空化图像引导超声介导的动脉粥样硬化药物输送

• 批准号: 8155319
• 负责人: Kevin Joseph Haworth
• 金额: $ 5.35万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8155319
• 关键词: Accounting; Acoustics; Air; Anti-Inflammatory Agents; Anti-inflammatory; Arterial Fatty Streak; Arteries; Atherosclerosis; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Cause of Death; Cessation of life; Clinical; Contrast Media; Cyclodextrins; Development; Direct Costs; Disease; Dose; Drug Delivery Systems; Drug Formulations; Elements; Encapsulated; Exposure to; Facilities and Administrative Costs; Family suidae; Feedback; Frequencies; Funding; Gases; Genes; Goals; Health Sciences; Image; In Vitro; Laboratories; Lipid Bilayers; Liposomes; Liquid substance; Maps; Measurement; Measures; Mechanical Stress; Mediating; Methods; Metric; Microbubbles; Modeling; Monitor; National Heart, Lung, and Blood Institute; Nature; Performance; Pharmaceutical Preparations; Phospholipids; Physiologic pulse; Physiological; Protocols documentation; Research; Scheme; Signal Transduction; Site; Solutions; Spatial Distribution; Staging; Techniques; Testing; Texas; Theoretical model; Therapeutic; Therapeutic Agents; Tissues; Translations; Ultrasonic Transducer; Ultrasonography; United States; United States National Institutes of Health; Universities; Use of New Techniques; Vascular Diseases; Vesicle; Work; aqueous; base; detector; improved; innovation; mortality; prevent; public health relevance; rosiglitazone; targeted delivery

DESCRIPTION (provided by applicant): Traditional means to identify and treat arterial disease are hampered by an inability to localize atheroma extent and composition. New techniques using targeted echogenic liposomes (ELIP) are being explored as possible solutions to overcome these problems. ELIP are phospholipid vesicles enclosing both aqueous and gaseous spaces. Therapeutics, such as drugs or genes, can be loaded into the ELIP. Furthermore, it has been seen that upon exposure to pulsed ultrasound, the therapeutic can be released from the ELIP and made available for delivery to nearby tissue. The encapsulated gas allows the ELIP to be imaged with a clinical ultrasound scanner and the therapeutic to be delivered via cavitation nucleation. The principal aim of this proposal is to develop techniques that will provide spatially resolved, noninvasive feedback for ultrasound-mediated delivery of a therapeutic to an arterial wall using ELIP. To achieve this aim, two specific aims will be investigated. 1) The acoustic emissions of insonified ELIP, as recorded by a passive ultrasound array, will be correlated with release of an anti-inflammatory (rosiglitazone-cyclodextrin). Subsequently, a spatial map of the emissions, and correlated therapeutic release, will be created. 2) Passive imaging of the insonified ELIP will be correlated with the delivery of the therapeutic to an ex vivo porcine artery. Successful completion of these studies will contribute significantly to the long-term goals of the Holland and McPherson Labs at the Universities of Cincinnati and Texas Health Sciences Center-Houston to trigger and enhance the delivery of a therapeutic for improved physiologic cardiovascular flow. PUBLIC HEALTH RELEVANCE: The proposal seeks to develop passive cavitation images for ultrasound-mediated local release and enhanced delivery of an anti-inflammatory drug for atheroma treatment using echogenic liposomes.

描述（由申请人提供）：识别和治疗动脉疾病的传统方法因无法定位动脉粥样硬化程度和成分而受阻。正在探索使用靶向回声脂质体（ELIP）的新技术作为克服这些问题的可能解决方案。ELIP是包封水和气体空间的磷脂囊泡。治疗药物，如药物或基因，可以加载到ELIP中。此外，已经看到，在暴露于脉冲超声时，治疗剂可以从ELIP释放并可用于递送到附近的组织。封装的气体允许ELIP用临床超声扫描仪成像，并通过空化成核输送治疗剂。该提案的主要目的是开发技术，将提供空间分辨，非侵入性的反馈，超声介导的治疗输送到动脉壁使用ELIP。为了实现这一目标，将研究两个具体目标。1)声穿透ELIP的声发射，如被动超声阵列所记录的，将与抗炎药（罗格列酮-环糊精）的释放相关。随后，将创建发射和相关治疗释放的空间图。2)声穿透ELIP的被动成像将与治疗剂向离体猪动脉的递送相关。这些研究的成功完成将大大有助于辛辛那提大学的Holland和麦克弗森实验室和德克萨斯健康科学中心-休斯顿的长期目标，以触发和增强改善生理心血管流量的治疗剂的输送。 公共卫生关系：该提案旨在开发被动空化图像，用于超声介导的局部释放和使用回声脂质体治疗动脉粥样硬化的抗炎药物的增强递送。